Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1 – 17 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Claim Objections
Claims 1 and 3 are objected to because of the following informalities: the claims seem to be missing the article “the” before “intracellular signaling domain” in line 3 of claim 1 and in line 1 of claim 3. Furthermore, claim 1 appears to be missing a linking verb, such as “is” or “was”, after “intracellular signaling domain” in line 3. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2 – 9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 2 – 9 recite the limitation "polypeptide" in the preamble of each claim. There is insufficient antecedent basis for this limitation in the claim. It seems that the preamble of each of claims 2 – 9 should recite “the CAR polypeptide”.
In addition, claim 3 recites “DAP12 backbone”, however, the specification does not provide a definition for a “DAP12 backbone” and it is not clear what the metes and bounds of this limitation are.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 – 5, 7, and 9 – 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by SHAH (WO 2017/214333-A1, published 01/31/2019; see PTO-892: Notice of References Cited).
The present application is directed to a chimeric antigen receptor (CAR) polypeptide, comprising an antigen binding domain, a transmembrane domain, an intracellular signaling domain, and an optional co- stimulatory signaling region, wherein intracellular signaling domain engineered to express at least one heterologous immunoreceptor tyrosine-based activation motif (ITAM).
SHAH is directed to CARs for cancer therapy. See abstract. SHAH teaches a CAR may have an ectodomain (extracellular), a transmembrane domain and an endodomain (intracellular). See paragraph 00132. SHAH teaches that the intracellular signaling domain is also known as cytoplasmic domain (see paragraph 00140) and that primary cytoplasmic signaling sequences that act in a stimulatory manner may contain signaling motifs which are known as immunoreceptor tyrosine-based activation motifs or ITAMs (see paragraph 00168).
Regarding claim 1, SHAH teaches a CAR with a CD33 antigen binding domain (“an antigen binding domain” as recited in claim 1), a transmembrane domain, an intracellular signaling domain, wherein the intracellular signaling domain expresses at least one heterologous immunoreceptor tyrosine-based activation motif (ITAM). See claim 1 and paragraph 00168.
Regarding claim 2, SHAH teaches that examples of ITAM-containing primary cytoplasmic signaling sequences include those derived from TCR zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD 3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d and that the cytoplasmic signaling molecule in CAR discloses comprises a cytoplasmic signaling sequence derived from CD3 zeta. See paragraph 00169.
Regarding claims 3 – 4, SHAH teaches that costimulatory domains include DAP12. See paragraph 00139.
Regarding claim 5, SHAH teaches CAR with a (a) a CD33 antigen binding domain; (b) a stalk domain; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; (e) a CD3 zeta signaling domain. See claim 1. SHAH teaches that the costimulatory signaling includes ITAM as discussed above, and SHAH further teaches that the CAR ectodomain, a signal peptide and that the signal peptide natively attached to the amino-terminal most component is used (e.g. in a scFv with orientation light chain - linker - heavy chain, the native signal of the light-chain is used). See paragraph 00132. Finally, SHAH teaches that the stalk domain can include a flexible hinge. See paragraph 00137 and claim 26. Thus, SHAH teaches the CAR polypeptide formula of SP-TAA-HG-TM-ISD-ITAM.
Regarding claims 7 and 9, SHAH teaches SEQ ID NO: 61 which comprises the DAP12 intracellular signaling domain backbone of SEQ ID NO:2, wherein the ITAM (present SEQ ID NO: 13 of present claim 9) is inserted into the backbone at amino acid position 19 of SEQ ID NO:2. See p. 102 and Appendix. The sequence of SEQ ID NO: 13 is in bold within the sequence of SEQ ID NO: 2 (see Alignment with SEQ ID NO:2 in the Appendix below).
Regarding claim 10, SHAH teaches an isolated nucleic acid encoding the disclosed CAR. See claims 1 – 13.
Regarding claim 11, SHAH teaches a vector comprising the nucleic acid sequence encoding the disclosed CAR. See claim 14.
Regarding claim 12, SHAH teaches an immune effector cell comprising a vector comprising the nucleic acid sequence encoding the disclosed CAR. See claims 36.
Regarding claims 13 and 15, SHAH teaches that the immune effector cell is a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell. See paragraph 00230.
Regarding claim 14, SHAH teaches adoptive T cell transfer and that an engineered antigen presenting cell (APC) may be used to propagate immune effector cells ex vivo. SHAH further teaches that immune effector cells can include both allogeneic and autologous sources. See paragraphs 00113, 0271, 0243.
Claims 1 – 5 and 8 – 15 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by FAN (WO 2021/037221-A1, filed 08/28/2020, published 03/04/2024; see PTO-892).
FAN is directed to a modified T cell with a functional exogenous receptor (CAR) comprising: (a) an extracellular ligand binding domain, (b) a transmembrane domain, and (c) an intracellular signaling domain (ISD) comprising a chimeric signaling domain (CMSD), wherein the CMSD comprises one or a plurality of Immune-receptor Tyrosine-based Activation Motifs (ITAMs), wherein the plurality of CMSD ITAMs are optionally connected by one or more linkers. See abstract, claim 1, and claim 15. FAN teaches that the functional exogenous receptor is a CAR (see claim 15) with an antigen-binding fragment (see claim 31). Thus, FAN teaches a CAR having the domains of present claim 1.
Regarding claim 2 - 4, FAN teaches that at least one of the CMSD ITAMs is derived from an ITAM-containing parent molecule selected from the group consisting of CD3ε, CD3δ, CD3γ, Igα (CD79a), Igβ (CD79b), FcεRIβ, FcεRIγ, DAP12, CNAIP/NFAM1, STAM-1, STAM-2, and Moesin. See p. 3, paragraph 8.
Regarding claim 5, FAN teaches a CAR (functional exogenous receptor) comprising (a) an extracellular ligand binding domain, (b) a transmembrane domain, and (c) an intracellular signaling domain (“ISD”) comprising a chimeric signaling domain (“CMSD”), wherein the CMSD comprises one or a plurality of immune-receptor Tyrosine-based Activation Motifs (“CMSD ITAMs”, wherein the plurality of CMSD ITAMs are optionally connected by one or more linkers (“CMSD linkers”). See claims 1 and 15. FAN further teaches a signal peptide located at the N-terminus of the functional exogenous receptor and that the functional exogenous receptor further comprises a hinge domain located between the C-terminus of the extracellular ligand binding domain and the N-terminus of the transmembrane domain. See p.11, paragraph 43. Thus, FAN teaches the CAR polypeptide formula SP-TAA-HG-TM-ISD-ITAM of claim 5.
Regarding claims 8 – 9, FAN teaches SEQ ID NOs: 4 and 8 comprising the claimed sequences of SEQ ID NOs: 3 and 13 with 100% identity. See Appendix.
Regarding claim 10, FAN teaches a nucleic acid encoding a functional exogenous receptor (e.g., ITAM-modified CAR). See claim 46 and p. 13, paragraph 49.
Regarding claim 11, FAN teaches a vector comprising the nucleic acid encoding a functional exogenous receptor (CAR). See claim 54.
Regarding claims 12 – 15, FAN teaches a method of producing a modified T cell (e.g., allogeneic T cell (as recited in present claim 14)), comprising introducing into a precursor T cell a nucleic acid encoding a functional exogenous receptor (e.g., ITAM-modified CAR), which may be on a vector (see p. 13, paragraph 49) as recited on present claim 12, and that the T cell is an NKT cell (see p. 162, paragraph 285) as recited in present claims 13 and 15.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 6 and 16 – 17 are rejected under 35 U.S.C. 103 as being unpatentable over SHAH as applied to claims 1 – 5, 7, and 9 – 15 above or over FAN as applied to claims 1 – 5 and 8 – 15 above, and further in view of ANG (WO 2019/023396-A1, published 01/31/2019; see PTO-892).
The teachings of FAN with regard to the claims are discussed above and fully incorporated here.
While FAN teaches the CAR structure with a transmembrane domain of the present claims, FAN does not expressly teach the transmembrane domain sequence of SEQ ID NO: 1
ANG is directed to enhanced chimeric antigen receptors (CARs). See paragraph 0003.
Regarding claim 6, ANG discloses the transmembrane domain of SEQ ID NO: 1 with 100% identity in SEQ ID NO: 52. See Appendix.
Because SHAH teaches a CAR structure that is effective at treating cancer and ANG teaches the sequence of a transmembrane domain that is also effective at treating cancer, it would have been obvious to modify SHAH’s CAR with the transmembrane sequence of ANG to arrive to the invention of claim 6. There would have been a reasonable expectation of success considering that a CAR with the structure and transmembrane domain of present claims is known to effectively treat cancer as evidenced by the applied prior art.
Regarding claims 16 – 17, ANG teaches that the skilled artisan will understand that additional immunotherapies may be used in combination or in conjunction with the disclosed methods (see paragraph 00191) and that the immunotherapy may be an immune checkpoint inhibitor targeting the PD-1 axis and/or CTLA-4 (see paragraph 00195), which may be an antibody (see paragraph 00196).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ESTELLA M. GUSTILO whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:00 AM - 5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JANET L. EPPS-SMITH can be reached at 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment with SEQ ID NO: 1
RESULT 15
BGB40184
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
ID BGB40184 standard; protein; 73 AA.
XX
AC BGB40184;
XX
DT 21-MAR-2019 (first entry)
XX
DE CAR construction related DAP12 protein, SEQ ID 52.
XX
KW DAP12 protein; DNAX-activation protein 12; autoimmune disease; cancer;
KW graft versus host disease; immune disorder; immunomodulator;
KW immunotherapy; inflammatory disease; therapeutic; transplant rejection.
XX
OS Unidentified.
XX
CC PN WO2019023396-A1.
XX
CC PD 31-JAN-2019.
XX
CC PF 25-JUL-2018; 2018WO-US043779.
XX
PR 25-JUL-2017; 2017US-0536934P.
XX
CC PA (TEXA ) UNIV TEXAS SYSTEM.
XX
CC PI Ang SO, Liu E, Shpall E, Rezvani K;
XX
DR WPI; 2019-12480D/12.
DR N-PSDB; BGB40183.
XX
CC PT Chimeric antigen receptor comprises truncated epidermal growth factor
CC PT receptor variant III in hinge of Chimeric antigen receptor, and where Ev3
CC PT hinge links extracellular domain and one intracellular signaling domain.
XX
CC PS Disclosure; SEQ ID NO 52; 143pp; English.
XX
CC The present invention relates to a chimeric antigen receptor (CAR),
CC useful for treating immune-related disorder. The CAR molecule comprises a
CC truncated epidermal growth factor receptor variant III (Ev3) in hinge of
CC the chimeric antigen receptor, where Ev3 hinge links to an extracellular
CC domain and an intracellular signaling domain. The invention further
CC relates to: (1) an isolated antigen-specific humanized single chain
CC variable fragment (scFv); (2) an isolated polynucleotide encoding an
CC isolated humanized scFv; (3) an expression vector, which comprises
CC isolated polynucleotide; (4) an isolated nucleic acid, which comprises a
CC nucleotide sequence encoding the CAR; (5) a host cell engineered to
CC express a CAR; (6) a pharmaceutical composition, which comprises
CC population of cells; (7) a composition, which comprises the population of
CC cells; and (8) a method for treating an immune-related disorder in a
CC subject. The chimeric antigen receptor used for treating immune-related
CC disorder such as cancer, autoimmune disorder, graft versus host disease,
CC allograft rejection, or inflammatory condition. The present sequence is a
CC DAP12 protein, useful for constructing a chimeric antigen receptor.
XX
SQ Sequence 73 AA;
Query Match 100.0%; Score 94; Length 73;
Best Local Similarity 100.0%;
Matches 21; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GVLAGIVMGDLVLTVLIALAV 21
|||||||||||||||||||||
Db 1 GVLAGIVMGDLVLTVLIALAV 21
Alignment with SEQ ID NO: 3
BJA36021
ID BJA36021 standard; peptide; 29 AA.
XX
AC BJA36021;
XX
DT 15-APR-2021 (first entry)
XX
DE CD3 zeta immune-receptor tyrosine-based activation motif (ITAM) 1, SEQ 4.
XX
KW CD3 zeta protein; T-cell CD3 glycoprotein zeta chain; cancer; cytostatic;
KW pharmaceutical; t-lymphocyte; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2021037221-A1.
XX
CC PD 04-MAR-2021.
XX
CC PF 28-AUG-2020; 2020WO-CN112181.
XX
PR 28-AUG-2019; 2019WO-CN103041.
PR 16-DEC-2019; 2019WO-CN125681.
XX
CC PA (NANJ-) NANJING LEGEND BIOTECH CO LTD.
XX
CC PI Fan X, Zhao Y, Wang B, Yu D, Huang X, Wang P, Zhuang Q;
XX
DR WPI; 2021-22204F/025.
XX
CC PT Modified T cell for pharmaceutical composition for treating a disease in
CC PT an individual, where disease is cancer, comprises an exogenous Nef
CC PT protein and a functional exogenous receptor comprising an extracellular
CC PT ligand binding domain.
XX
CC PS Disclosure; SEQ ID NO 4; 292pp; English.
XX
CC The invention relates to a novel modified T cell, useful in
CC pharmaceutical composition for treating disease. The invention further
CC claims: 1) a method for producing a modified T cell; 2) a method for
CC treating a disease in an individual; 3) a vector, which comprises a first
CC nucleic acid encoding an exogenous Nef protein and a second nucleic acid
CC encoding a functional exogenous receptor; and 4) a non-naturally
CC occurring Nef protein. The modified T cell for pharmaceutical composition
CC for treating a disease such as cancer.
XX
SQ Sequence 29 AA;
ALIGNMENT:
Query Match 100.0%; Score 153; Length 29;
Best Local Similarity 100.0%;
Matches 29; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APAYQQGQNQLYNELNLGRREEYDVLDKR 29
|||||||||||||||||||||||||||||
Db 1 APAYQQGQNQLYNELNLGRREEYDVLDKR 29
Alignment with SEQ ID NO: 2
RESULT 17
BES30562
(NOTE: this sequence has 164 duplicates in the database searched.
See complete list at the end of this report)
ID BES30562 standard; protein; 52 AA.
XX
AC BES30562;
XX
DT 08-FEB-2018 (first entry)
XX
DE DNAX-activation protein 12 (DAP12) signaling domain, SEQ:61.
XX
KW DAP12 protein; DNAX activation protein 12;
KW TYRO tyrosine kinase binding protein; acute myelogenous leukemia;
KW cell proliferation; chimeric antigen receptor; cytostatic;
KW hematological-gen.; immune stimulation; recombinant protein;
KW t-lymphocyte; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2017214333-A1.
XX
CC PD 14-DEC-2017.
XX
CC PF 07-JUN-2017; 2017WO-US036440.
XX
PR 08-JUN-2016; 2016US-0347503P.
XX
CC PA (INXN ) INTREXON CORP.
XX
CC PI Shah RR, Chan T, Emtage P, Yarlagadda R;
XX
DR WPI; 2017-853117/01.
DR N-PSDB; BES30561.
XX
CC PT Isolated nucleic acid for encoding chimeric antigen receptor for treating
CC PT acute myeloid leukemia, comprises cluster of differntiation antigen
CC PT binding domain, transmembrane domain, costimulatory signaling domain and
CC PT CD3 zeta signaling domain.
XX
CC PS Disclosure; SEQ ID NO 61; 189pp; English.
XX
CC The present invention relates to an isolated nucleic acid encoding a
CC chimeric antigen receptor (CAR). The CAR comprises: (a) a CD33 antigen
CC binding domain; (b) a stalk domain; (c) a CD8 alpha transmembrane (TM)
CC domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or
CC both; and (e) a CD3 zeta signaling domain, where the antigen binding
CC domain comprises a single chain antibody fragment (scFv) comprising a
CC light chain variable region (VL) and heavy chain variable region (VH).
CC The invention further discloses: (1) a vector comprising a backbone and a
CC nucleic acid sequence, which encodes a truncated epidermal growth factor
CC receptor (EGFR) comprising one of HER1t, HER1t-1 or a functional variant
CC and the chimeric antigen receptor; (2) a vector comprising the backbone
CC and a nucleic acid sequence encoding a full length CD20, a truncated CD20
CC (CD20t-1) or a functional variant and the chimeric antigen receptor (CAR)
CC ; (3) an immune effector cell comprising the nucleotide and vector; (4) a
CC method for stimulating a T cell-mediated immune response to a target cell
CC population or tissue in a human subject, which involves administering an
CC effective amount of a cell genetically modified to express a CAR to human
CC subject; (5) a system for expressing the CAR in an immune effector cell,
CC which comprises one or more vectors encoding the isolated nucleic acid;
CC (6) a method for expressing the CAR in an immune effector cell, which
CC involves contacting the immune effector cell with the system; and (7) a
CC method for stimulating the proliferation and/or survival of engineered T-
CC cells, which involves: (i) obtaining a sample of cells from a subject,
CC where the sample comprises T-cells or T-cell progenitors; (ii)
CC transfecting the cells with one or more vectors encoding the isolated
CC nucleic acid; and culturing the population of CD33 CAR T-cells ex vivo
CC for 2 days or less. The CAR encoding isolated nucleic acid of the
CC invention is useful for stimulating a T cell-mediated immune response to
CC a target cell and for stimulating the proliferation and/or survival of
CC engineered T-cells for treating acute myeloid leukemia (AML). The present
CC sequence represents a DNAX-activation protein 12 (DAP12) signaling domain
CC which is used in constructing the CAR.
XX
SQ Sequence 52 AA;
Query Match 79.9%; Score 97.5; Length 52;
Best Local Similarity 44.2%;
Matches 23; Conservative 0; Mismatches 0; Indels 29; Gaps 1;
Qy 1 YFLGRLVPRGRGAAEAAT-----------------------------RPYYK 23
|||||||||||||||||| |||||
Db 1 YFLGRLVPRGRGAAEAATRKQRITETESPYQELQGQRSDVYSDLNTQRPYYK 52
Alignment with SEQ ID NO: 13
RESULT 8
BES30562
(NOTE: this sequence has 164 duplicates in the database searched.
See complete list at the end of this report)
ID BES30562 standard; protein; 52 AA.
XX
AC BES30562;
XX
DT 08-FEB-2018 (first entry)
XX
DE DNAX-activation protein 12 (DAP12) signaling domain, SEQ:61.
XX
KW DAP12 protein; DNAX activation protein 12;
KW TYRO tyrosine kinase binding protein; acute myelogenous leukemia;
KW cell proliferation; chimeric antigen receptor; cytostatic;
KW hematological-gen.; immune stimulation; recombinant protein;
KW t-lymphocyte; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2017214333-A1.
XX
CC PD 14-DEC-2017.
XX
CC PF 07-JUN-2017; 2017WO-US036440.
XX
PR 08-JUN-2016; 2016US-0347503P.
XX
CC PA (INXN ) INTREXON CORP.
XX
CC PI Shah RR, Chan T, Emtage P, Yarlagadda R;
XX
DR WPI; 2017-853117/01.
DR N-PSDB; BES30561.
XX
CC PT Isolated nucleic acid for encoding chimeric antigen receptor for treating
CC PT acute myeloid leukemia, comprises cluster of differntiation antigen
CC PT binding domain, transmembrane domain, costimulatory signaling domain and
CC PT CD3 zeta signaling domain.
XX
CC PS Disclosure; SEQ ID NO 61; 189pp; English.
XX
CC The present invention relates to an isolated nucleic acid encoding a
CC chimeric antigen receptor (CAR). The CAR comprises: (a) a CD33 antigen
CC binding domain; (b) a stalk domain; (c) a CD8 alpha transmembrane (TM)
CC domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or
CC both; and (e) a CD3 zeta signaling domain, where the antigen binding
CC domain comprises a single chain antibody fragment (scFv) comprising a
CC light chain variable region (VL) and heavy chain variable region (VH).
CC The invention further discloses: (1) a vector comprising a backbone and a
CC nucleic acid sequence, which encodes a truncated epidermal growth factor
CC receptor (EGFR) comprising one of HER1t, HER1t-1 or a functional variant
CC and the chimeric antigen receptor; (2) a vector comprising the backbone
CC and a nucleic acid sequence encoding a full length CD20, a truncated CD20
CC (CD20t-1) or a functional variant and the chimeric antigen receptor (CAR)
CC ; (3) an immune effector cell comprising the nucleotide and vector; (4) a
CC method for stimulating a T cell-mediated immune response to a target cell
CC population or tissue in a human subject, which involves administering an
CC effective amount of a cell genetically modified to express a CAR to human
CC subject; (5) a system for expressing the CAR in an immune effector cell,
CC which comprises one or more vectors encoding the isolated nucleic acid;
CC (6) a method for expressing the CAR in an immune effector cell, which
CC involves contacting the immune effector cell with the system; and (7) a
CC method for stimulating the proliferation and/or survival of engineered T-
CC cells, which involves: (i) obtaining a sample of cells from a subject,
CC where the sample comprises T-cells or T-cell progenitors; (ii)
CC transfecting the cells with one or more vectors encoding the isolated
CC nucleic acid; and culturing the population of CD33 CAR T-cells ex vivo
CC for 2 days or less. The CAR encoding isolated nucleic acid of the
CC invention is useful for stimulating a T cell-mediated immune response to
CC a target cell and for stimulating the proliferation and/or survival of
CC engineered T-cells for treating acute myeloid leukemia (AML). The present
CC sequence represents a DNAX-activation protein 12 (DAP12) signaling domain
CC which is used in constructing the CAR.
XX
SQ Sequence 52 AA;
Query Match 100.0%; Score 148; Length 52;
Best Local Similarity 100.0%;
Matches 29; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RKQRITETESPYQELQGQRSDVYSDLNTQ 29
|||||||||||||||||||||||||||||
Db 19 RKQRITETESPYQELQGQRSDVYSDLNTQ 47
RESULT 1
BJA36025
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
ID BJA36025 standard; peptide; 29 AA.
XX
AC BJA36025;
XX
DT 15-APR-2021 (first entry)
XX
DE DAP12 immune-receptor tyrosine-based activation motif (ITAM) SEQ 8.
XX
KW DAP12 protein; cancer; cytostatic; pharmaceutical; t-lymphocyte;
KW therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2021037221-A1.
XX
CC PD 04-MAR-2021.
XX
CC PF 28-AUG-2020; 2020WO-CN112181.
XX
PR 28-AUG-2019; 2019WO-CN103041.
PR 16-DEC-2019; 2019WO-CN125681.
XX
CC PA (NANJ-) NANJING LEGEND BIOTECH CO LTD.
XX
CC PI Fan X, Zhao Y, Wang B, Yu D, Huang X, Wang P, Zhuang Q;
XX
DR WPI; 2021-22204F/025.
XX
CC PT Modified T cell for pharmaceutical composition for treating a disease in
CC PT an individual, where disease is cancer, comprises an exogenous Nef
CC PT protein and a functional exogenous receptor comprising an extracellular
CC PT ligand binding domain.
XX
CC PS Disclosure; SEQ ID NO 8; 292pp; English.
XX
CC The invention relates to a novel modified T cell, useful in
CC pharmaceutical composition for treating disease. The invention further
CC claims: 1) a method for producing a modified T cell; 2) a method for
CC treating a disease in an individual; 3) a vector, which comprises a first
CC nucleic acid encoding an exogenous Nef protein and a second nucleic acid
CC encoding a functional exogenous receptor; and 4) a non-naturally
CC occurring Nef protein. The modified T cell for pharmaceutical composition
CC for treating a disease such as cancer.
XX
SQ Sequence 29 AA;
Query Match 100.0%; Score 148; Length 29;
Best Local Similarity 100.0%;
Matches 29; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RKQRITETESPYQELQGQRSDVYSDLNTQ 29
|||||||||||||||||||||||||||||
Db 1 RKQRITETESPYQELQGQRSDVYSDLNTQ 29